Photodynamic therapy (PDT) has proven to be very effective in destroying abnormal tissue such as cancer cells. In this therapy, a photosensitizer agent having a characteristic light absorption waveband is first administered to the patient, typically either orally or by injection. Abnormal tissue in the body is known to selectively absorb certain photosensitizer agents to a much greater extent than normal tissue, e.g., tumors of the pancreas and colon may absorb two to three times the volume of these agents, compared to normal tissue. Even more effective selectivity can be achieved using a photoreactive agent that is bound to an antibody, which links with antigens on targeted cells. The cancerous or abnormal tissue that has absorbed or linked with the photosensitizer dye is then destroyed by administering light of an appropriate wavelength or waveband corresponding to the absorption wavelength or waveband of the photosensitizer agent.
To administer PDT to internal cancerous lesions that are not accessible through a natural body orifice, a fiber optic probe is typically inserted either through a needle or through a surgically created opening. The internal cancerous lesions are visually located by imaging the treatment site through the fiber optic system so that light from a laser source can be accurately directed through the optical fiber to destroy the abnormal tissue. Even when the internal treatment site is accessible through natural body orifices, an endoscope is usually required to visualize the lesion and accurately direct the light therapy administered to the treatment site. The invasive placement of an optical fiber probe or endoscope at an internal treatment site exposes a patient to potential risks associated with bleeding, infection, and the use of anesthesia and sedation.
Clearly, it would be preferable to administer PDT to an internal treatment site using a non-invasive approach in which light from an external source is applied to the intact dermal layer overlying an internal treatment site and penetrates the overlying tissue sufficiently to destroy the abnormal cells at the treatment site. The prior art describes the use of externally applied light for PDT, which is typically emitted by lamps, lasers, light emitting diodes (LEDs), and laser diode arrays, but in the past, PDT has been employed primarily to treat relatively superficial cutaneous treatment sites, e.g., for treatment of skin lesions, and generally has not been widely used for treating sub-dermal diseased tissue.
Light of longer wavelengths (e.g., longer than 700 nm) is able to penetrate dermal tissue sufficiently to reach internal treatment sites, where tumors may be disposed. A two photon absorption system for administering PDT to treat metastasized cancer cells is described in commonly assigned U.S. Pat. No. 5,957,960 (U.S. Ser. No. 08/850,909, filed May 5, 1997, which has been allowed). However, this and other systems disclosed in the prior art for administering PDT with an externally applied light source are not particularly useful for targeting specific small and large volume tumors.
One of the problems with administering light therapy to an internal treatment site with an externally applied light source relates to the difficulty in accurately directing the light through the overlying tissue, since the disposition of the internal treatment site is normally not visually apparent to the medical practitioner. However, it is possible to employ various imaging systems to identify the location of abnormal tissue within a patient's body, including its depth below the dermal layer. Suitable imaging systems capable of imaging soft tissue structures to locate internal diseased sites include ultrasound probes and gamma probes. By viewing the images of the patient's internal body structure, it is possible to determine an appropriate position, direction, and depth at which to focus light of an appropriate waveband at a position on the patient's skin. However, it would be inconvenient to implement an imaging procedure to locate a treatment site and then position one or more external light sources to focus on the site thus found. Due to movement of the patient's body (both internal and external) that will typically occur after the imaging procedure is completed, it is likely that the light may be inaccurately focused on the internal treatment site identified by the imaging process. Instead, it would be preferable to provide an integral light therapy device that includes a light source and an imaging probe, so that the light is more accurately focused on and administered to the treatment site identified and located by the imaging probe. In addition, an imaging probe that is an integral part of the apparatus used to administer light therapy can monitor the effects of the light therapy in real time, without interrupting the therapy. It may be particularly important to monitor the status of an internal treatment site during a period of light therapy that extends over several hours, since the therapy may cause changes in the site being treated that should be noted by the medical practitioner.
If an imaging system is used to determine the depth at which light from multiple sources is focused during the administration of PDT, it will also be necessary to provide a mechanism for altering the focal point and/or the direction in which the light is directed. Use of plural light sources will probably be preferable in most cases, since the intensity of the light from a single source passing through tissue overlying the treatment site will be much less than the intensity of the light from all of the plurality of light sources at the point of intersection at the internal treatment site. Accordingly, the adverse impact of the light therapy on normal tissue will be minimized, because the intensity of the light from a single source will be below the threshold necessary to activate the photosensitizer agent, particularly at the lower concentration of the drug in normal tissue. Furthermore, by varying the direction in which light emitted by selected light sources penetrates the patient's body, it should be possible to apply the light therapy at an internal treatment site in conformance with the shape and dimension of the abnormal tissue or tumor. Thus, the light might be directed into the body to encompass an elongate tumor in one patient, and a smaller, more spherical tumor in another patient, or to treat different portions of an irregularly-shaped tumor in yet another patient.
The advantages provided by a system and method for administering light therapy that includes an imaging device are also applicable for rendering light therapy to treat non-oncologic conditions such as atherosclerotic and infectious disease. The imaging probe can provide a much more accurate basis for directing the light therapy at internal sites to destroy diseased tissue or to inhibit the growth of undesirable organisms.